By contrast, there is no significant correlation between the expression of either marker and the clinicopathological patient characteristics in diffuse-type GC. according to Laurn. Moreover, patients who grouped as positive for expression of v3 on endothelial cells, and patients with an intestinal type GC, grouped as negative for expression of v5 on stroma cells, had significantly longer survival. The expression of v5 on stroma cells was confirmed to be an independent prognostic factor of intestinal-type GC. Conclusion The expression of v3 and v5 in at least one tumor component in all GC samples is an interesting new Lisinopril result that should form a basis for further investigations; for example, regarding selective integrin antagonists and the value of v3 and v5 as putative prognostic biomarkers. Moreover, both markers might be helpful in the routine classification of GC subtypes. Electronic supplementary material The online version of this article (doi:10.1007/s10120-014-0435-2) contains supplementary material, which is available to authorized users. or EpsteinCBarr virus and dietary and lifestyle factors contribute to the risk of developing GC. This progress has been accompanied by the introduction of chemotherapy for GC, which is evolving continuously and which Lisinopril has improved patients survival [1C3]. Evidence is accumulating that patient prognosis and treatment response depend not only on the tumor stage but also on tumor-specific alterations of both gene expression and various signaling pathways. The two major histological subtypes of GC according to Laurn, diffuse-type and intestinal-type GC, have distinct tumor dissemination patterns and show diverse pathogeneses and expression profiles, likely resulting from molecular differences in tumor epithelial and stroma cells [4, 5]. Although the distinction between diffuse and intestinal subtype in GC has prognostic significance, it is still widely neglected in patient-tailored treatment of GC [6, 7]. Integrins are a family of 24 heterodimeric, multifunctional glycoproteins. As cell adhesion molecules and cell surface receptors, they mediate cell-to-cell and cell to Lisinopril extracellular matrix interactions, and are involved in a great variety of physiological and pathological processes [8]. They are composed of an subunit, and a subunit that connect to the cytoskeleton and interact with multiple signaling pathways; the C combination determines integrin ligand binding specificity and intracellular signaling [9]. Integrins are important regulators of differentiation, tumor growth, survival, migration, and invasion. In malignant tumors, they are involved in several processes that characterize the tumor phenotype [10]. Several integrin heterodimers have already been shown to be involved in GC biology and to have a significant value as prognostic markers. An increased expression of integrin v6 is linked significantly with reduced survival, lymph node metastasis, and the number of cancer-associated fibroblasts, and integrin 51 is described to be significantly associated with tumor Lisinopril differentiation, TNM stage, and recurrence [11C15]. Recently, integrins, particularly v3 and v5, have been recognized as putative targets for the treatment of several cancers, which has spurred BMPR1B research on integrins in cancer biology [16C19]. Thus, the characterization of integrin distribution in human tumors is of great interest. At present little is known about the expression of integrins v3 and v5 in GC, mainly owing to the lack of antibodies suitable for use on formalin-fixed and paraffin-embedded (FFPE) tissue [20]. Only two studies to date have focused on integrins v3 and v5 in GC. Those studies differ significantly from our study, as they investigated only 19 and 55 cases, respectively, and relied on frozen tissue sections. Also, owing to the small number of cases, they were unable to correlate the expression pattern of v3 and v5 in GC with clinicopathological patient characteristics [12, 21]. Recently, comprehensive molecular characterization including whole-genome sequencing was performed in GC and nontumor pairs for integrative genomic analysis of GC [22, 23]: 20 of 26 genes of the integrin subunits were deregulated in GC pathways, involving also cell adherens junctions, angiogenesis, and focal adhesion. Thus, deregulation of integrin expression may be a tumor-biological hallmark of GC or its specific subtypes. However, data on integrin expression on a protein level in GC are still sparse, and validation of genomic data is urgently needed. Here we investigated the expression of v3 and v5 in GC on the protein level, examining the following questions: Are integrins expressed in GC? Are integrins implicated in GC biology? Do integrins discriminate the GC subtypes? Is the expression of integrins prognostically relevant? Materials and methods Lisinopril Study population From the archive of the Institute of Pathology, University Hospital.